New Psychoactive Substances Toxicity: A Systematic Review of Acute and Chronic Psychiatric Effects

Abstract

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae.

Keywords: bipolar disorder; hallucinations; mental disorders; new psychoactive substances; psychiatric symptoms; psychotic disorders; schizophrenia; substance-related disorders.

Figure 1

Prisma 2020 flow diagram of the search sources and strategy.

Figure 2

Chemical structures of NPSs involved in 109 related intoxications with acute or chronic psychiatric symptoms, categorized into classes. Abbreviations: MDPV, 3,4-methylenedioxypyrovalerone; MDPHP, 3,4-methylenedioxy-alpha-pyrrolidinohexanophenone; α-PVP, alpha-pyrrolidinovalerophenone; α-PHiP, α-pyrrolidinoisohexanophenone; α-PHP, α-pyrrolidinohexanophenone; Hex-en, N-ethyl-hexedrone; 4-MMC, mephedrone; 3-MeO-PCP, 1-[1-(3-methoxyphenyl)cyclohexyl]piperidine; MXE, methoxetamine; 5-IT, 1-(1H-indol-5-yl)propan-2-amine; BZP, 1-benzylpiperazine; 6-APB, 6-(2-Aminopropyl)benzofuran.